Jan 29 Creating a New Genetic Code

For the first time ever, scientists have successfully expanded the previously universal genetic code that governs the growth and characteristics of all organisms in nature. This genetic code, found in the form of DNA, has always been composed of four key nitrogenous bases – adenine, thymine, cytosine, and guanine (abbreviated A, T, C, and G). The research group working out of The Scripps Research Institute in California, however, were able to extend the genetic alphabet through the addition of two new nitrogenous bases, known as X and Y. The new bases were inserted into E. coli bacteria and replicated, without fault, over the course of 60 generations. Professor Floyd Romesberg, the leading member of the team, believes this “semisynthetic organism… suggests that all of life’s processes can be subject to manipulation” [1].

Romesberg and his team attempted a similar experiment back in 2014, but the semisynthetic organism failed to grow sufficiently and repeatedly lost the artificial nitrogenous bases. They made three significant changes to their approach in an effort to manufacture bacteria that could survive indefinitely while maintaining a genetic code consisting of six bases.

The initial change involved manipulating the nucleotide transporter responsible for inserting the new bases, X and Y, into the bacteria’s DNA. Without a functioning transporter, it would be impossible for X and Y to actually integrate into the genetic code and have any potential effect. Yorke Zhang, a member of Romesberg’s team, explained that “the transporter was used in the 2014 study, but it made the semisynthetic organism very sick” [3]. Minor modifications to the transporter’s toxicity allowed for the E. coli to effectively maintain its uptake of X and Y throughout growth and replication, an important requirement “if the semisynthetic organism is going to really be an organism” [1].

The second important change involved manipulating the Y base in order to increase its recognition during replication and thus promote its integration into growing DNA molecules. Romesberg’s team achieved this through “a more chemically optimized [unnatural base pair]” that increased the bacteria’s ability to interact with the new Y base [3].

Finally, the team used a genome editing tool, known as CRISPR-Cas9, to target cells without the new X and Y bases for destruction. Essentially, the bacteria were trained “to see a genetic sequence without X and Y as a foreign invader” [2]. This third step functioned as an insurance policy against the possibility of X and Y not being incorporated into the bacteria’s DNA, as it eliminated the population of cells grown incorrectly. With all the changes in place and functioning successfully, Romesberg’s team concluded that “this [semi-synthetic organism] is thus a form of life that can stably store genetic information using a six-letter, three base-pair alphabet” [3].

The full range of capabilities accorded to this semisynthetic organism remain to be explored. Romesberg’s team believes the primary function of this expanded genetic code will be to introduce new information into organisms through nitrogenous bases that are actually readable. From there, “the work could lead to bugs that can help manufacture new classes of drugs to treat disease” [1]. The team also believes that the methods they have discovered are currently only applicable to simple organisms, such as the E. coli bacteria used in this experiment. While the future remains unclear at this time, Romesberg is confident that “this will blow open what we can do with proteins” [4].

With any attempt to adjust the genetic code comes serious ethical questions, and those have been prevalent ever since Romesberg’s team published their 2014 study in which they failed to successfully integrate the X and Y bases into E. coli’s genetic code. Certain groups believe this research leads to “safety concerns and questions about whether humans are playing God” [5]. Jim Thomas works for the ETC Group, which investigates the “socioeconomic and ecological issues surrounding new technologies” [6]. Thomas depicts Romesberg’s semisynthetic organism as an “unprecedented ‘alien’ life form” with undeniable “ethical, legal, and regulatory implications” [5]. How soon it will be before such implications are addressed remains to be seen, as Thomas notes the government’s current lack of “oversight, assessment, or regulation for this surging field” [5]. The delay between experimentation and regulation is inevitable given the nature of scientific discovery, but the extent to which any supervisory institution places guidelines or limits on this area of research is surely contingent upon the potential of semisynthetic organisms to benefit or harm current life forms on Earth. Any concerns that these new organisms could go rogue and escape beyond control are unfounded, according to Romesberg. He claims the semisynthetic organisms could “never infect something” because their replication is contingent upon the supply of X and Y bases [5]. That supply comes directly from Romesberg’s team during the experiment, meaning the bacteria would quickly die without the resources of the laboratory. Despite these assurances, Romesberg is conscious that misinterpretation of this new technology could lead to unreasonable opposition, and he urges that “the benefits need to be weighed against the potential costs” [7].

While improved treatments for disease is undoubtedly enticing, such promises are entirely theoretical until further work is done. In the meantime, as with any budding focus of scientific research, it is crucial that caution is combined with enthusiasm to ensure sensible progress. Any effort to “create organisms with wholly unnatural attributes and traits not found elsewhere in nature”, which is Romesberg’s depiction of future development, necessitates a response to fundamental ethical questions before dangerous boundaries are crossed [3].

Crew, Bec. "New Organisms Have Been Formed Using the First Ever 6-Letter Genetic Code." ScienceAlert. January 24, 2017. Accessed January 25, 2017. http://www.sciencealert.com/new-organisms-have-been-formed-using-the-first-ever-6-letter-genetic-code.

Sample, Ian. "Organisms created with synthetic DNA pave way for entirely new life forms." The Guardian. January 24, 2017. Accessed January 25, 2017. https://www.theguardian.com/science/2017/jan/23/organisms-created-with-synthetic-dna-pave-way-for-new-entirely-new-life-forms?CMP=oth_b-aplnews_d-3.

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